All animal PET/CT and tissue biodistribution. Future work will expand

All animal PET/CT and tissue biodistribution. Future work will expand the approach to perform longitudinal imaging studies focused on intra-medullary tumor lesions in mouse models of mouse and human MM. Additionally, we will evaluate VLA-4 expression as a marker of effective therapy by molecular imaging, and the results will be compared with the existing imaging standards such as FDG-PET/CT and MRI.Supporting InformationFigure S1 Small animal PET/CT images showing high tumor uptake at early and late time points. Representative maximum intensity projection (MIP) images of the same mousePET iImaging of Multiple Myelomabearing matrigel assisted s.c. 5TGM1 tumor in the nape of the neck at 2 h and 24 h post injection. Over time, the tumor to background ratios are improved as 23977191 the radioactive probe clears out from non-target organs. (TIF)histology. We thank Professors Samuel Achilefu (Director, Optical Pleuromutilin custom synthesis Radiology Laboratory) and Ravi Vij (Vice Chair, Multiple Myeloma Research Consortium) for helpful discussions.Author ContributionsConceived and designed the experiments: MS DS MJ CJA MHT. Performed the experiments: MS DS MJ. Analyzed the data: MS DS MJ MH AZ KNW CJA MHT. Contributed reagents/materials/analysis tools: MS DS MH KNW CJA MHT. Wrote the paper: MS DS.AcknowledgmentsWe thank Washington University’s small animal imaging facility personnel for assistance with animal biodistribution and imaging experiments. We thank Prof. Deborah Novak and Ms. Crystal Idleburg for assistance withThere are approximately 400 million people worldwide who are chronically infected with hepatitis B virus (HBV), of whom 75 live in the Asia-Pacific region. Chronic hepatitis B results in liver disease progressing to cirrhosis and hepatocellular carcinoma (HCC) and is responsible for approximately one million liverrelated deaths per annum [1]. Treatment of HBV involves finite administration of pegylated or unpegylated interferon alfa, or indefinite administration of anti-HBV nucleoside/nucleotide analogues. Five such analogues are currently available. Lamivudine, a deoxycytidine analogue, was the first nucleoside approved for use in HBV and lamivudine monotherapy remains common despite high rates of treatment-emergent drug resistance [2]. Entecavir is a deoxyguanosine analogue with a high genetic barrier to resistance in treatment-naive patients [3]. However, lamivudine resistance predisposes HBV to subsequent entecavir resistance [4]. Telbivudine is an L-deoxythymidine analogue with superior efficacy to lamivudine [5] but a similar resistance profile [6]. Finally, the nucleotides adefovir and tenofovir are both acyclic mimetics of deoxyadenosine monophosphate which retain activity against lamivudine- and telbivudine-resistant HBV [6]. However, adefovir is associated with dose-dependent nephrotoxicity which restricts its dosing to 10 mg daily [7], at which dose it demonstrates inferior virologic efficacy to the other agents [8?0]. There are also concerns about the long-term safety of tenofovir, which is associated with significant loss of renal function in HIV treatment [11]. HBV viral Indolactam V replication is a key driver for disease progression and is associated with the development of cirrhosis and HCC [12]. The initial goal of treatment is to suppress viral replication; thereafter, sustained (on-treatment) or maintained (off-treatment) suppression of circulating HBV DNA is associated with improved serological responses and long-term outcomes [13,14]. The emergence of dr.All animal PET/CT and tissue biodistribution. Future work will expand the approach to perform longitudinal imaging studies focused on intra-medullary tumor lesions in mouse models of mouse and human MM. Additionally, we will evaluate VLA-4 expression as a marker of effective therapy by molecular imaging, and the results will be compared with the existing imaging standards such as FDG-PET/CT and MRI.Supporting InformationFigure S1 Small animal PET/CT images showing high tumor uptake at early and late time points. Representative maximum intensity projection (MIP) images of the same mousePET iImaging of Multiple Myelomabearing matrigel assisted s.c. 5TGM1 tumor in the nape of the neck at 2 h and 24 h post injection. Over time, the tumor to background ratios are improved as 23977191 the radioactive probe clears out from non-target organs. (TIF)histology. We thank Professors Samuel Achilefu (Director, Optical Radiology Laboratory) and Ravi Vij (Vice Chair, Multiple Myeloma Research Consortium) for helpful discussions.Author ContributionsConceived and designed the experiments: MS DS MJ CJA MHT. Performed the experiments: MS DS MJ. Analyzed the data: MS DS MJ MH AZ KNW CJA MHT. Contributed reagents/materials/analysis tools: MS DS MH KNW CJA MHT. Wrote the paper: MS DS.AcknowledgmentsWe thank Washington University’s small animal imaging facility personnel for assistance with animal biodistribution and imaging experiments. We thank Prof. Deborah Novak and Ms. Crystal Idleburg for assistance withThere are approximately 400 million people worldwide who are chronically infected with hepatitis B virus (HBV), of whom 75 live in the Asia-Pacific region. Chronic hepatitis B results in liver disease progressing to cirrhosis and hepatocellular carcinoma (HCC) and is responsible for approximately one million liverrelated deaths per annum [1]. Treatment of HBV involves finite administration of pegylated or unpegylated interferon alfa, or indefinite administration of anti-HBV nucleoside/nucleotide analogues. Five such analogues are currently available. Lamivudine, a deoxycytidine analogue, was the first nucleoside approved for use in HBV and lamivudine monotherapy remains common despite high rates of treatment-emergent drug resistance [2]. Entecavir is a deoxyguanosine analogue with a high genetic barrier to resistance in treatment-naive patients [3]. However, lamivudine resistance predisposes HBV to subsequent entecavir resistance [4]. Telbivudine is an L-deoxythymidine analogue with superior efficacy to lamivudine [5] but a similar resistance profile [6]. Finally, the nucleotides adefovir and tenofovir are both acyclic mimetics of deoxyadenosine monophosphate which retain activity against lamivudine- and telbivudine-resistant HBV [6]. However, adefovir is associated with dose-dependent nephrotoxicity which restricts its dosing to 10 mg daily [7], at which dose it demonstrates inferior virologic efficacy to the other agents [8?0]. There are also concerns about the long-term safety of tenofovir, which is associated with significant loss of renal function in HIV treatment [11]. HBV viral replication is a key driver for disease progression and is associated with the development of cirrhosis and HCC [12]. The initial goal of treatment is to suppress viral replication; thereafter, sustained (on-treatment) or maintained (off-treatment) suppression of circulating HBV DNA is associated with improved serological responses and long-term outcomes [13,14]. The emergence of dr.